反应详情

A disposable tube fitted with a septum was charged with (Z)—N′-(5-(4-chlorophenyl)-3,3,6,7-tetramethyl-1H-thieno[2,3-e][1,4]diazepin-2(3H)-ylidene)acetohydrazide (112 mg, 0.288 mmol) and tetrahydrofuran (10 mL). Tosic acid (75 mg, 0.394 mmol, 1.4 equiv) was added, and the solution as stirred at room temperature 30 min, at which point LC/MS analysis indicated complete consumption of the starting material. The solution was concentrated for purification by column chromatography (eluting with dichloromethane/methanol/ammonium hydroxide) to yield an off-white amorphous solid. This solid was further purified by semi-prep HPLC (water/acetonitrile/0.1% trifluoroacetic acid), free-based with a strong cation exchange solid phase extraction column (eluting with ammonia in methanol), and lyophilized to yield 4-(4-chlorophenyl)-2,3,6,6,9-pentamethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine as a yellow amorphous solid (m/z=371) (46 mg, 43%). 1H NMR (400 MHz; DMSO): δ 7.48 (s, 4H), 2.60 (s, 3H), 2.39 (s, 3H), 1.97 (s, 3H), 1.57 (s, 3H), 1.07 (s, 3H).

1. customA disposable tube fitted with a septum
2. customconsumption of the starting material
3. concentrationThe solution was concentrated for purification by column chromatography (eluting with dichloromethane/methanol/ammonium hydroxide)
4. customto yield an off-white amorphous solid
5. customThis solid was further purified by semi-prep HPLC (water/acetonitrile/0.1% trifluoroacetic acid), free-based with a strong cation exchange solid phase extraction column (eluting with ammonia in methanol)